Periodontal disease is the most common infectious disease of middle-aged adults. Treponema denticola is an oral, bacterial species that is strongly associated with the development of periodontitis. The periodontal pocket, the site of infection between the tooth and the gums, is bathed in crevicular fluid containing antimicrobial peptides, immunoglobulin and highly abundant complement proteins. Complement is an innate immune system that can kill Gram-negative bacteria, mark pathogens for destruction, and modulate local inflammation. T. denticola can evade complement- mediated destruction by production of FhbB and dentilisin. FhbB binds the host negative complement regulator factor H and is critical to the survival of the bacterium in human serum. Dentilisin is capable of cleaving the central complement components C3 and C3b as well as factor H. T. denticola may cause a dysregulation of the local immune response leading to inflammation-associated tissue damage that is a hallmark of periodontitis. This project aims to sequence fhbB from a variety of clinical isolates of T. denticola then apply biochemical approaches such as recombinant protein expression and purification, surface plasmon resonance, immunoblotting and allelic exchange to determine if protein sequence variation affects the FhbB:FH interaction and protective function. Additionally, this study aims to identify a dentilisin generated factor H fragment, which remains bound to the cell, by purification and mass spectrometry. Several biochemical and cell culture techniques will be applied to determine if the factor H fragment retains regulatory activity, can protect T. denticola from complement destruction, and alter host cell binding of full length FH. A more complete picture of immune dysregulation caused by T. denticola during periodontal infection will aid in potential future therapeutic and vaccine design.